Physiological Appearance of Hybrid FDG-Positron Emission Tomography/Computed Tomography Imaging Following Uncomplicated Endovascular Aneurysm Sealing Using the Nellix Endoprosthesis

Purpose: To investigate the physiological uptake of hybrid fluorine-18-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) before and after an uncomplicated endovascular aneurysm sealing (EVAS) procedure as a possible tool to diagnose EVAS graft infection and differentiate from postimplantation syndrome. Materials and Methods: Eight consecutive male patients (median age 78 years) scheduled for elective EVAS were included in the prospective study (ClinicalTrials.gov identifier NCT02349100). FDG-PET/CT scans were performed in all patients before the procedure and 6 weeks after EVAS. The abdominal aorta was analyzed in 4 regions: suprarenal, infrarenal neck, aneurysm sac, and iliac. The following parameters were obtained for each region: standard uptake value (SUV), tissue to background ratio (TBR), and visual examination of FDG uptake to ascertain its distribution. Demographic data were obtained from medical files and scored based on reporting standards. Results: Visual examination showed no difference between pre- and postprocedure FDG uptake, which was homogenous. In the suprarenal region no significant pre- and postprocedure differences were observed for the SUV and TBR parameters. The infrarenal neck region showed a significant decrease in the SUV and no significant decrease in the TBR. The aneurysm sac and iliac regions both showed a significant decrease in SUV and TBR between the pre- and postprocedure scans. Conclusion: Physiological FDG uptake after EVAS was stable or decreased with regard to the preprocedure measurements. Future research is needed to assess the applicability and cutoff values of FDG-PET/CT scanning to detect endograft infection after EVAS

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Mitophagy plays a central role in mitochondrial ageing

The mechanisms underlying ageing have been discussed for decades, and advances in molecular and cell biology of the last three decades have accelerated research in this area. Over this period, it has become clear that mitochondrial function, which plays a major role in many cellular pathways from ATP production to nuclear gene expression and epigenetics alterations, declines with age. The emerging concepts suggest novel mechanisms, involving mtDNA quality, mitochondrial dynamics or mitochondrial quality control. In this review, we discuss the impact of mitochondria in the ageing process, the role of mitochondria in reactive oxygen species production, in nuclear gene expression, the accumulation of mtDNA damage and the importance of mitochondrial dynamics and recycling. Declining mitophagy (mitochondrial quality control) may be an important component of human ageing

Endograft Conformability in Fenestrated Endovascular Aneurysm Repair for Complex Abdominal Aortic Aneurysms

Purpose:To compare the impact of 2 commercially available custom-made fenestrated endografts on patient anatomy.Materials and Methods:The records of 234 patients who underwent fenestrated endovascular aneurysm repair for abdominal aortic aneurysm from March 2002 to July 2016 in 2 hospitals were screened to identify those who had pre- and postoperative computed tomography angiography assessments with a slice thickness o

Evaluation of Electrocardiogram-Gated Computed Tomography Angiography to Quantify Changes in Geometry and Dynamic Behavior during the Cardiac Cycle of the Nellix Endovascular Sealing System

Background. The Nellix endovascular sealing system (EVAS) was a unique concept with regard to its sealing concept that failed, related to high migration rates. We investigated the changes in aortoiliac morphology during the cardiac cycle before and after EVAS using electrocardiography (ECG)-gated CT. Methods. Eight patients scheduled for EVAS were prospectively enrolled. ECG-gated CT scans were made pre- and postoperatively. Measurements were performed in the mid-systolic and mid-diastolic phases. Endpoints were changes in infrarenal aortoiliac morphology postoperatively compared to preoperatively and their changes in the cardiac cycle. Results. Both pre- and postoperatively, there were no changes during the cardiac cycle. EVAS caused an increase in neck diameter and surface in both phases (). EVAS increased the luminal AAA volume (), with a decrease in thrombus volume () in both phases and an increase in total volume () in the systolic phase. During follow-up, one patient presented with >5 mm migration. There were no differences in the movements of this patient compared to the remaining patients. Conclusion. The cardiac cycle had a very limited effect on the aortoiliac dynamics before and after EVAS and, therefore, there is probably not a role for ECG-gated CT in enhanced surveillance programs. EVAS itself has a significant impact on anatomy, particularly the neck diameter, length, and volumes of the AAA

Early results with the custom-made Fenestrated Anaconda aortic cuff in the treatment of complex abdominal aortic aneurysm

Objective: The objective of this study was to investigate the feasibility of a specific custom-made fenestrated aortic cuff in the treatment of complex abdominal aortic aneurysms (AAAs). Methods: Between 2013 and 2016, a total of 57 custom-made Fenestrated Anaconda (Vascutek, Inchinnan, Scotland, UK) aortic cuffs were placed in 38 centers worldwide. All centers were invited to participate in this retrospective analysis. Postoperative and follow-up data included the presence of adverse events, necessity for reintervention, and renal function. Results: Fifteen clinics participated, leading to 29 cases. Median age at operation was 74 years (interquartile range [IQR], 71-78 years); five patients were female. Two patients were treated for a para-anastomotic AAA after open AAA repair, 19 patients were treated because of a complicated course after primary endovascular AAA repair, and 8 cases were primary procedures for AAA. A total of 76 fenestrations (mean, 2.6 per case) were used. Four patients needed seven adjunctive procedures. Two patients underwent conversion, one because of a dissection of the superior mesenteric artery and one because of perforation of a renal artery. Median operation time was 225 minutes (IQR, 150-260 minutes); median blood loss, 200 mL (IQR, 100-500 mL); and median contrast volume, 150 mL (IQR, 92-260 mL). Primary technical success was achieved in 86% and secondary technical success in 93%. The 30-day morbidity was 7 of 29 with amortality rate of 4 of 29. Estimated glomerular filtration rate remained unchanged before and after surgery (76 to 77 mL/min/m(2)). Between preoperative and median follow-up of 11 months, estimated glomerular filtration rate was reduced statistically significantly (76 to 63 mL/min/m(2)). During follow-up, 9 cases had an increase in aneurysm sac diameter (5 cases > 5 mm); 14 cases had a stable or decreased aneurysm sac diameter; and in 2 cases, no aneurysm size was reported. No type I endoleak was reported, and two cases with a type III endoleak were treated by endovascular means during follow-up. Survival, reintervention-free survival, and target vessel patency at 1 year were 81% +/- 8%, 75% +/- 9%, and 99% +/- 1%, respectively. After 2 years, these numbers were 81% +/- 8%, 67% +/- 11%, and 88% +/- 6%, respectively. During follow-up, the two patients with a type III endoleak needed endograft-related reinterventions. Conclusions: Treatment with this specific custom-made fenestrated aortic cuff is feasible after complicated previous (endovascular) aortic repair or in complex AAAs. The complexity of certain AAA cases is underlined in this study, and the Fenestrated Anaconda aortic cuff is a valid option in selected cases in which few treatment options are left

Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? Study protocol of the SCRaTCH-OFO trial: a randomized controlled trial

BackgroundIn the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault >30%) are advised to perform timed intercourse for at least another 6months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility.MethodA multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12months.DiscussionSeveral small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conceptio

Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? : Study protocol of the SCRaTCH-OFO trial: a randomized controlled trial

BACKGROUND: In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called 'endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility. METHOD: A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception  30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months. DISCUSSION: Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception < 12 months. TRIAL REGISTRATION: NTR6687 , registered August 31st, 2017. PROTOCOL VERSION: Version 2.6, November 14th, 2018